Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT05229991 |
Other study ID # |
SOR-0527-20-CTIL |
Secondary ID |
SCRC20042 |
Status |
Active, not recruiting |
Phase |
Phase 3
|
First received |
|
Last updated |
|
Start date |
May 15, 2021 |
Est. completion date |
April 30, 2025 |
Study information
Verified date |
May 2023 |
Source |
Soroka University Medical Center |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Open label, single arm, multi-center clinical trial of lonafarnib 50 mg QD plus ritonavir 200
mg QD, administered orally, over a 48-week treatment period, with a 24-week post-treatment
follow-up period, in patients with chronic Hepatitis D Virusinfection.
Objectives: To evaluate the safety and tolerability of once daily dosing of lonafarnib 50 mg
with ritonavir 200 mg over a 48-week treatment period.
To evaluate the effect of once daily dosing of lonafarnib 50 mg with ritonavir 200 mg over a
48-week treatment period with a 24-week post-treatment follow-up on HDV viral levels.
Trial population: Up to 30 patients with chronic HDV infection with detectable HDV RNA and
compensated liver disease.
Description:
Background: Hepatitis D virus (HDV) was identified as the infectious agent causing viral
hepatitis in the presence of hepatitis B virus (HBV). While HDV can replicate autonomously
inside the hepatocyte, the virus requires co-infection with HBV to complete virion assembly
and to facilitate transmission. HDV causes the most severe form of viral hepatitis, with
rapid progression to cirrhosis and high rates of development of hepatocellular carcinoma.
Currently there are no FDA approved therapies for chronic HDV infection (CHD) which presents
an unmet medical need. The off-label use of pegylated interferon alpha (Alpha) for the
treatment of CHD has so far been explored in several small single-arm studies and in 2
randomized controlled clinical trials, showing limited efficacy and high relapse rates. In
addition, Alpha is associated with a poor tolerability profile and its use is limited in
patients with advanced disease.
Lonafarnib (LNF), a FT inhibitor has been evaluated in over 2,000 subjects in clinical
studies, comprising more than fifty Phase 1 and Phase 2 studies and two Phase 3 studies, with
healthy subjects and patients with HDV, cancer, Hutchinson-Gilford progeria syndrome (HGPS)
and progeroid laminopathies. Treatment with LNF has been administered as continuous (up to 11
years in HGPS) and intermittent therapy (exceeding one year in cancer patients).
The use of LNF in CHD has been assessed in a proof of concept study, a series of four phase 2
clinical trials (the LOWR program) and an on-going phase 3 clinical trial (D-LIVR study).
Hypothesis: that treatment with LNF50/RTV200 QD for 48 weeks will be safe and lead to a
reduction in HDV RNA levels at end of treatment and end of follow up.
Procedures: At baseline, systems review, physical examination, vital signs (temperature,
blood pressure, pulse rate per minute), anthropometric measurements (weight, height and BMI)
and ECG will be performed. Information regarding the use of alcohol and drugs, symptoms and
use of concomitant medications collected. Blood will be drawn for testing of local CBC,
chemistry, coagulation studies, HDV antibody and RNA levels, HCV antibody (& RNA if
necessary), HBsAg levels, HBeAg status, HBV DNA levels, liver elastography and ultrasound.
All blood tests besides HDV RNA levels, will be performed at a local lab. HDV RNA level
testing will be performed at a central laboratory. Pregnancy test will be performed in
females of child-bearing potential. Trial medications will be dispensed. Use of anti-HBV
therapy (tenofovir or entecavir) will be confirmed.
Follow up visits will be conducted at week 4, 12, 24, 36 and 48 of treatment and at 24 weeks
after stopping treatment and will include systems review, ECG recordings, evaluation of
concomitant medications use, adverse events monitoring and assessment of compliance with
trial medications and anti HBV therapy. In addition, blood will be drawn for measurement of
CBC, chemistry panel, coagulation tests and HDV RNA and HBV DNA levels at each visit. Trial
medications will be dispensed at each visit during the treatment phase of trial.
Adverse events and concomitant medications will be collected throughout the trial.
Data to capture:
- Demographic data: Gender, age, ethnicity, country of birth
- Detailed medical history: including currently prescribed medications, recently
administered medications, dispensing date, past medications use and dispensing date,
past medical diagnosis including diagnosis date, past medical procedures including
procedure date, allergies.
- Habits: history of recreational drugs and alcohol consumption (using CAGE
questionnaire).
- Clinical evaluation: Systems review, anthropometric measurements (weight, height and
BMI), physical examination, vital signs, symptom questionnaire and AE assessment.
- Blood tests: Complete blood count, biochemistry panel, coagulation tests, anti-HDV
antibody, anti HCV antibody, HDV RNA, HBV DNA.
Safety data collected during the trial (e.g., AEs and laboratory test results) will be
monitored on an ongoing basis by the trial team.